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Nature Nov 2021The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development....
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
Topics: Adolescent; Aged, 80 and over; Animals; Child; Child Development; Estrous Cycle; Female; Homozygote; Humans; Hypothalamus; Insulin-Like Growth Factor I; Male; Melanocortins; Menarche; Mice; Nutritional Status; Phenotype; Puberty; Receptor, Melanocortin, Type 3; Sexual Maturation; Time Factors; Weight Gain
PubMed: 34732894
DOI: 10.1038/s41586-021-04088-9 -
Journal of Cystic Fibrosis : Official... Oct 2019Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the... (Review)
Review
Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the majority of individuals with CF. However, youth with more severe disease are still at risk for delayed puberty. Careful evaluation of pubertal development in children and adolescents with CF is important as pubertal timing impacts linear growth, bone mineral accrual, body image and psychosocial wellbeing, all of which can also be impacted directly by CF. This article reviews the physiology of puberty, timing of puberty in CF, evaluation of pubertal development, and the differential diagnosis, evaluation, and management of delayed and precocious puberty in people with CF.
Topics: Adolescent; Child; Cystic Fibrosis; Diagnosis, Differential; Female; Humans; Male; Puberty; Puberty, Delayed
PubMed: 31679734
DOI: 10.1016/j.jcf.2019.08.013 -
Best Practice & Research. Clinical... Jan 2022Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset... (Review)
Review
Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Pubertal onset is regulated by genetic, nutritional, environmental, and socio-economic factors. Disturbances affecting pubertal timing result in adverse health conditions later in life. Human genetic studies show that around 50-80% of the variation in pubertal onset is genetically determined. The genetic control of pubertal timing has been a field of active investigation in attempt to better understand the neuroendocrine control of this relevant period of life. Large populational studies and patient cohort-based studies have provided insights into the genetic regulation of pubertal onset. In this review, we discuss these discoveries and discuss potential mechanisms for how implicated genes may affect pubertal timing.
Topics: Gonadotropin-Releasing Hormone; Humans; Puberty; Puberty, Delayed; Sexual Maturation
PubMed: 35183440
DOI: 10.1016/j.beem.2022.101618 -
Current Opinion in Pediatrics Aug 2020Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when... (Review)
Review
PURPOSE OF REVIEW
Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair.
RECENT FINDINGS
The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta.
SUMMARY
The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.
Topics: Adrenal Glands; Adrenarche; Androgens; Child; Child Development; Dehydroepiandrosterone Sulfate; Female; Humans; Pregnancy; Puberty; Puberty, Precocious; Steroids; Zona Reticularis
PubMed: 32692055
DOI: 10.1097/MOP.0000000000000928 -
Obesity Reviews : An Official Journal... Jun 2020In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed... (Review)
Review
In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in childhood obesity and puberty onset variability.
Topics: Adipokines; Adolescent; Child; Female; Humans; Male; Pediatric Obesity; Puberty
PubMed: 32003144
DOI: 10.1111/obr.13005 -
Reproduction (Cambridge, England) Feb 2023Sex differences in the gut microbiome may impact multiple aspects of human health and disease. In this study, we review the evidence for microbial sex differences in... (Review)
Review
IN BRIEF
Sex differences in the gut microbiome may impact multiple aspects of human health and disease. In this study, we review the evidence for microbial sex differences in puberty and adulthood and discuss potential mechanisms driving differentiation of the sex-specific gut microbiome.
ABSTRACT
In humans, the gut microbiome is strongly implicated in numerous sex-specific physiological processes and diseases. Given this, it is important to understand how sex differentiation of the gut microbiome occurs and how these differences contribute to host health and disease. While it is commonly believed that the gut microbiome stabilizes after 3 years of age, our review of the literature found considerable evidence that the gut microbiome continues to mature during and after puberty in a sex-dependent manner. We also review the intriguing, though sparse, literature on potential mechanisms by which host sex may influence the gut microbiome, and vice versa, via sex steroids, bile acids, and the immune system. We conclude that the evidence for the existence of a sex-specific gut microbiome is strong but that there is a dearth of research on how host-microbe interactions lead to this differentiation. Finally, we discuss the types of future studies needed to understand the processes driving the maturation of sex-specific microbial communities and the interplay between gut microbiota, host sex, and human health.
Topics: Female; Humans; Male; Adult; Gastrointestinal Microbiome; Bile Acids and Salts; Puberty
PubMed: 36445259
DOI: 10.1530/REP-22-0303 -
Clinical Endocrinology Oct 2022The timing of pubertal development is strongly influenced by the genetic background, and clinical presentations of delayed puberty are often found within families with... (Review)
Review
The timing of pubertal development is strongly influenced by the genetic background, and clinical presentations of delayed puberty are often found within families with clear patterns of inheritance. The discovery of the underlying genetic regulators of such conditions, in recent years through next generation sequencing, has advanced the understanding of the pathogenesis of disorders of pubertal timing and the potential for genetic testing to assist diagnosis for patients with these conditions. This review covers the significant advances in the understanding of the biological mechanisms of delayed puberty that have occurred in the last two decades.
Topics: Humans; Hypogonadism; Puberty; Puberty, Delayed
PubMed: 34617615
DOI: 10.1111/cen.14606 -
Journal of Sleep Research Jun 2023Sleep health tends to worsen during adolescence, partially due to pubertal-related changes that, in combination with social and psychological factors, can lead to...
Sleep health tends to worsen during adolescence, partially due to pubertal-related changes that, in combination with social and psychological factors, can lead to long-lasting impairments in sleep health and affective functioning. Discrepant findings between subjective and objective measures of sleep in relation to affect have been reported in studies of adults; however, few investigations have assessed both subjective and objective sleep quality in a single sample, and fewer have examined this in the context of pubertal development. We aimed to (1) characterise pubertal associations with subjective sleep satisfaction, objective sleep efficiency, and objective and subjective sleep duration in adolescents; (2) examine the longitudinal association between daily affect and sleep metrics; and (3) test whether pubertal stage moderated this association. Eighty-nine participants (64% female, ages 13-20) completed an ecological momentary assessment (EMA) and actigraphy protocol. Independent of age, advanced pubertal stage was associated with lower subjective sleep satisfaction but not with objective sleep indices. Subjective sleep satisfaction was associated with within-person trajectories of negative affect, but not with positive affect. Pubertal stage and sleep satisfaction did not interact to predict within-day negative or positive affect. These findings are consistent with previous reports showing that objective and subjective sleep health are associated differently with puberty, and that subjective sleep health is associated with daily affect. Pubertal stage may be a more important indicator of subjective sleep quality in adolescence than is chronological age, most likely due to hormonal changes and psychological adjustment to the physical changes associated with the pubertal transition.
Topics: Adult; Humans; Adolescent; Female; Male; Sleep; Puberty; Sleep Initiation and Maintenance Disorders; Sleep Quality; Sleep Duration; Actigraphy
PubMed: 36514260
DOI: 10.1111/jsr.13805 -
Journal of Medical Ethics Nov 2020
Topics: Humans; Puberty
PubMed: 33033114
DOI: 10.1136/medethics-2020-106822 -
Frontiers in Endocrinology 2023Levels of steroid hormones in the first three months of life, a period referred to as 'mini-puberty', are one of the earliest physiological differences between typical...
BACKGROUND
Levels of steroid hormones in the first three months of life, a period referred to as 'mini-puberty', are one of the earliest physiological differences between typical males and females postnatally. Autistic traits also show consistent typical sex differences in later infancy, after the 18 month of life. Previous studies have shown testosterone is associated with later levels of autistic traits. Studies testing if postnatal testosterone levels are associated with autistic traits have reported null results. No studies to date have investigated mini-puberty longitudinally or tested for interactions with baseline sex differences or familial likelihood of autism.
METHODS
The 'Cambridge Human Imaging and Longitudinal Development Study' (CHILD) is a prospective enriched cohort study in Cambridge, UK. It includes physiological measurements in early infancy, as well as neurodevelopmental follow-ups over the first two years of life. A subset of the cohort also includes children with a family history of autism (a diagnosed parent or sibling). Salivary testosterone levels were assessed at two time-points, just after the 2 and 6 month of life. Autistic traits were measured using the Quantitative Checklist of Autism in Toddlers (Q-CHAT) when the children were 18 months of age.
RESULTS
Salivary testosterone levels were significantly higher during 'mini-puberty' in the 2 and 3 month of life, compared to after the 6 month of life, in both males and females. There was no significant sex difference at either time-point. Log-transformed testosterone levels were not associated with autistic traits (Q-CHAT). There was no interaction effect with infant sex, autism family history or baseline testosterone levels after mini-puberty (at >6 months of age).
CONCLUSION
Both male and female infants have elevated levels of salivary testosterone during mini-puberty but in this relatively small sample this was not associated with their later autistic traits at 18 months or their family history of autism. This suggests that rather than postnatal testosterone levels are more relevant for understanding the causes of autism. Future studies should test these relationships in larger samples.
Topics: Pregnancy; Humans; Male; Female; Infant; Testosterone; Autistic Disorder; Cohort Studies; Prospective Studies; Puberty
PubMed: 37091846
DOI: 10.3389/fendo.2023.1126023